By Dr. Geoffrey Modest
A new study highlights how rapidly the field of Hepatitis C management is progressing, moving from an interferon-free therapy to one that is now also ribavirin-free (see Gastroenterology 2015; 149: 971).
Details:
- Open-label international study of 82 patients without cirrhosis (42 treatment-naive and 40 prior null responders) and 99 with cirrhosis (47 treatment-naive and 52 treatment-experienced with prior relapse, or a null or partial response). The demographics varied some between these different groups, but overall approx 50% male, 85% white, mean age 55, in non-cirrhotic patients –> 60% with fibrosis score F0-F1, 25% F2, 13% F3). All with genotype 1b infection. 68-95% had non-CC IL28B genotype (this may not be clinically relevant, but this genotype did portend a less favorable response to perinterferon/ribavirin treatment).
- Treated with ombitasvir 25mg (a NS5A replication complex inhibitor), paritaprevir 150mg (an NS3/4A protease inhibitor), and ritonavir 100mg once daily for 12 weeks (if no cirrhosis) or 24 weeks (with cirrhosis). [Note: This is the same combo in the pill Viekira, minus dabasuvir 250mg]
- Primary endpoint: sustained viral response at 12 weeks after the end of treatment (SVR12)
Results:
- Without cirrhosis: treatment-naive had SVR12 of 95.2%, null responders had SVR12 of 90.0%
- With cirrhosis: treatment-naive had SVR12 of 97.9%, treatment-experienced had SVR12 of 96.2%
- Virologic relapse happened in 3 null responders without cirrhosis and 1 with cirrhosis
- Virologic breakthrough occurred in 1 null responder without cirrhosis
- Adverse events (varied by assigned group) included headache (17-33%), asthenia (5-21%), pruritis (0-17%), and diarrhea (0-15%). Almost all were “mild”. Serious adverse effects in 7 patients (1 each): extrusion of penile prosthesis, COPD exacerbation, esophageal variceal hemorrhage, humerus fracture and partial seizures, elevate ALT and AST levels (this patient stopped drugs for days 20-36, but then was able to resume and had an SVR12), peripheral artery aneurysm and hepatic neoplasm. Only one patient discontinued meds because of an adverse effect (isolated peripheral edema which resolved after study drug cessation)
- One interesting sideline of the study: there were detectable RAVs (resistance-associated variants), mostly to NS5A (17.6%) as well as NS3 (1.1%). but there was no association between these baseline RAVs and response to therapy (though all 4 of those with virologic relapse and the 1 with virologic breakthrough did have RAVs in both NS3 and NS5A at the time of failure)
So, what does this all mean? There are evolving therapies which are working on larger groups of people (treatment-naive or not, cirrhotic or not), which seem to have high barrier to clinical resistance, and with fewer meds causing adverse effects (ribavirin in this case). The landscape is changing quickly, and there is increasing hope of developing an interferon and ribavirin-free, pangenotypic, single pill therapy (at least this is much more likely than developing a reasonable-cost therapy). And, as with HIV treatment, the newer regimens are simpler, more effective, and have many fewer adverse effects. Which means that we in primary care are in increasingly good positions to take care of patients with these infections as part of taking care of the whole patient.